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央广网昆明10月11日消息(记者李健飞)近日,中国科学院昆明动物研究所神经发育与进化研究组在BMP信号传导及脊椎动物早期神经发育研究中取得进展,首次揭示了脊椎动物中高度保守的小核蛋白ZC4H2调控BMP信号通路的分子机制及其在脊椎动物早期神经系统发育中的功能。该研究成果于8月16日在线发表在英国皇家学会官方生物学期刊Open Biology上。
脊椎动物神经系统的发育包括神经诱导、图式形成以及神经分化三个主要过程。在脊椎动物早期胚胎发育的原肠运动后期,部分外胚层组织在BMP信号通路抑制性因子的作用下被诱导形成神经板,该过程即为神经诱导过程,是神经系统发育的起始。神经板组织经过后续的图式形成以及神经分化阶段最终形成复杂的神经系统。
ZC4H2是一个非常保守的小核蛋白,与人类神经系统相关疾病的发生密切相关,但关于其在神经系统发育中的功能一直未知。昆明动物所神经发育与进化学科组的研究发现:在非洲爪蛙的胚胎发育过程中,ZC4H2是一个母源性表达的基因,随后在发育中的神经系统中特异表达。功能实验表明,ZC4H2参与了非洲爪蛙早期胚胎神经诱导过程;且体内和体外的实验都证明,ZC4H2可以正调控BMP信号通路。进一步的生化实验表明,ZC4H2通过直接与Smad1/5蛋白相互作用,竞争性抑制了其与泛素连接酶Smurf1/2的结合,从而抑制了Smad1/5蛋白的泛素化降解途径进而促进了其蛋白稳定性。此外,在对人类神经系统相关疾病中鉴定出的ZC4H2的突变研究中发现,ZC4H2可能是通过对BMP信号通路的调控参与了人类神经系统的发育过程。
昆明动物所助理研究员马鹏程、昆明动物所与安徽大学联合培养硕士生任碧玉、昆明动物所博士研究生杨相彩为文章的共同第一作者,昆明动物所研究员毛炳宇和马鹏程为文章共同通讯作者。该项研究工作得到了国家自然科学基金委、中科院以及云南省的资助。
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